1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N³-((7-(R)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine | 1037624-76-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N³-((7-(R)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine
• 英文别名: (R)-1-(6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-C]pyridazin-3-YL)-N3-(7-(pyrrolidin-1-YL)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-YL)-1H-1,2,4-triazole-3,5-diamine；1-(3,4-diazatricyclo[9.4.0.02,7]pentadeca-1(15),2,4,6,11,13-hexaen-5-yl)-3-N-[(7R)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine
• CAS: 1037624-76-2
• 化学式: C₃₀H₃₄N₈
• 分子量: 506.654
• InChiKey: KXMZDGSRSGHMMK-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  phenyl N'-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)carbamimidate 、 3-hydrazino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine 以 异丙醇 为溶剂， 反应 18.0h， 以to provide enantiomerically pure 1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-(7-(R)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine as a yellow solid (0.04 g, 50%)的产率得到1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N³-((7-(R)-pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine
  参考文献：
  名称：

  POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS

  摘要：

  本发明揭示了多环杂芳基取代的三唑类化合物及含有该化合物的制药组合物，用于抑制受体蛋白酪氨酸激酶Axl的活性。还揭示了使用该化合物治疗与Axl活性相关的疾病或病况的方法。

  公开号：

  US20080188455A1

文献信息

• AXL INHIBITORS FOR USE IN COMBINATION THERAPY FOR PREVENTING, TREATING OR MANAGING METASTATIC CANCER
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US20190336500A1

  公开（公告）日：2019-11-07

  This invention is directed to methods of preventing, treating or managing cancer, preferably metastatic cancer, in a patient. The methods comprise administering an effective amount of an Axl inhibitor in combination with the administration of an effective amount of one or more chemotherapeutic agents.

  这项发明旨在针对患者预防、治疗或管理癌症，最好是转移性癌症的方法。该方法包括在给予有效剂量的Axl抑制剂的同时，联合给予一个或多个化疗药物的有效剂量。
• POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
  申请人：RIGEL PHARMACEUTICALS, INC.

  公开号：US20140323490A1

  公开（公告）日：2014-10-30

  Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

  本发明涉及多环杂芳基取代的三唑化合物以及含有这些化合物的制药组合物，这些化合物被揭示为在抑制受体蛋白酪氨酸激酶Axl的活性方面有用。还揭示了使用这些化合物治疗与Axl活性相关的疾病或病状的方法。
• POLYCYCLIC HETEROARYL SUBSTITUTED TRIAZOLES USEFUL AS AXL INHIBITORS
  申请人：Goff Dane

  公开号：US20080188455A1

  公开（公告）日：2008-08-07

  Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

  本发明揭示了多环杂芳基取代的三唑类化合物及含有该化合物的制药组合物，用于抑制受体蛋白酪氨酸激酶Axl的活性。还揭示了使用该化合物治疗与Axl活性相关的疾病或病况的方法。
• Polycyclic heteroaryl substituted triazoles useful as Axl inhibitors
  申请人：Rigel Pharmaceuticals, Inc.

  公开号：US08168636B2

  公开（公告）日：2012-05-01

  Polycyclic heteroaryl substituted triazoles and pharmaceutical compositions containing the compounds are disclosed as being useful in inhibiting the activity of the receptor protein tyrosine kinase Axl. Methods of using the compounds in treating diseases or conditions associated with Axl activity are also disclosed.

  本文披露了多环杂芳基取代的三唑和含有该化合物的药物组合物，其可用于抑制受体蛋白酪氨酸激酶Axl的活性。同时，本文还披露了使用该化合物治疗与Axl活性相关的疾病或病况的方法。
• COMBINATION THERAPY
  申请人：BerGenBio ASA

  公开号：EP3804723A1

  公开（公告）日：2021-04-14

  The present invention concerns an Axl inhibitor and one or more immune checkpoint (activity) modulators and/or one or more oncolytic viruses, for use in the prevention, treatment or management of cancer, wherein the Axl inhibitor and the one or more immune checkpoint (activity) modulators and/or the one or more oncolytic viruses are administered concurrently, separately or sequentially; compositions containing such components in combination; and methods of treating cancer in a patient by administering such components in combination.

  本发明涉及一种Axl抑制剂和一种或多种免疫检查点（活性）调节剂和/或一种或多种溶瘤病毒，用于预防、治疗或控制癌症，其中Axl抑制剂和一种或多种免疫检查点（活性）调节剂和/或一种或多种溶瘤病毒同时、分别或依次给药；含有这些成分的组合物；以及通过联合给药这些成分治疗患者癌症的方法。